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Study of the effect of PU-H71 on increasing radiosensitivity of cervical cancer cells
Wang Jiankai1, Miao Guoying1, Wang Wenjuan2, Hu Yongguo1, Cai Hongyi1
1Department of Radiation Oncology,Gansu Provincial Hospital, Lanzhou 730000, China; 2Physical Examination Center, Gansu Third People's Hospital, Lanzhou 730000, China
AbstractObjective To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells. Methods The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair. Conclusion PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.
Wang Jiankai,Miao Guoying,Wang Wenjuan et al. Study of the effect of PU-H71 on increasing radiosensitivity of cervical cancer cells[J]. Chinese Journal of Radiation Oncology, 2023, 32(6): 551-556.
Wang Jiankai,Miao Guoying,Wang Wenjuan et al. Study of the effect of PU-H71 on increasing radiosensitivity of cervical cancer cells[J]. Chinese Journal of Radiation Oncology, 2023, 32(6): 551-556.
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2023, Vol. 32 
